Subchronic endotoxin inhalation causes persistent airway disease
Subchronic endotoxin inhalation causes persistent airway disease
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DOI：
10.1152/ajplung.00001.2003
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发表时间：
2003-09-01
影响因子：
4.9
通讯作者：
Schwartz, DA
中科院分区：
文献类型：
--
作者：
Brass, DM;Savov, JD;Schwartz, DA
有机粉尘中的内毒素成分可引起急性可逆性气流阻塞和气道炎症。为了验证内毒素单独引起气道重塑的假设，我们比较了两种近交系小鼠对亚慢性内毒素暴露的反应。在内毒素敏感（C3 HeB/FeJ）和内毒素抗性（C3 H/HeJ）小鼠中暴露于内毒素[脂多糖（LPS）] 1天、5天或8周后评价生理和生物学参数。LPS暴露5天或8周后，只有C3 HeB/FeJ对吸入乙酰甲胆碱的气道高反应性升高。仅C3 HeB/FeJ小鼠在LPS暴露1天、5天或8周后具有显著的下呼吸道炎症。小，中，大气道的体视学测量结果表明，8周暴露于LPS导致扩张的粘膜下区域仅在C3 HeB/FeJ小鼠。通过溴脱氧尿苷掺入测量的细胞增殖有助于粘膜下层的扩张，并且仅在主动暴露于LPS的C3 HeB/FeJ小鼠中显著升高。C3 HeB/FeJ小鼠在LPS暴露1天和5天后全肺灌洗液中的白细胞介素-1 β蛋白水平显著升高，并且在LPS暴露5天后全肺灌洗液中的总转化生长因子-β 1和活性转化生长因子-β 1蛋白水平显著升高。我们的研究结果表明，亚慢性吸入LPS的结果在持续气道疾病的发展，内毒素反应性小鼠。
The endotoxin component of organic dusts causes acute reversible airflow obstruction and airway inflammation. To test the hypothesis that endotoxin alone causes airway remodeling, we have compared the response of two inbred mouse strains to subchronic endotoxin exposure. Physiological and biological parameters were evaluated after 1 day, 5 days, or 8 wk of exposure to endotoxin [ lipopolysaccharide (LPS)] in endotoxin-sensitive (C3HeB/FeJ) and endotoxin-resistant (C3H/HeJ) mice. After 5 days or 8 wk of LPS exposure, only C3HeB/FeJ had elevated airway hyperreactivity to inhaled methacholine. Only the C3HeB/FeJ mice had significant inflammation of the lower respiratory tract after 1 day, 5 days, or 8 wk of LPS exposure. Stereological measurements of small, medium, and large airways indicated that an 8-wk exposure to LPS resulted in expansion of the submucosal area only in the C3HeB/FeJ mice. Cell proliferation as measured by bromodeoxyuridine incorporation contributed to the expansion of the submucosa and was only significantly elevated in C3HeB/FeJ mice actively exposed to LPS. C3HeB/FeJ mice had significantly elevated levels of interleukin-1beta protein in whole lung lavage after 1 day and 5 days of LPS exposure and significantly elevated protein levels of total and active transforming growth factor-beta1 in whole lung lavage fluid after 5 days of LPS exposure. Our findings demonstrate that subchronic inhalation of LPS results in the development of persistent airway disease in endotoxin-responsive mice.